The first self-hardening calcium phosphate cements (CPCs) were developed in our laboratory under the present and a previous N1H grant. One such CPC material has been in clinical use since 1996 for repairing cranial defects in humans. In recent years, several additional CPCs have been approved by the FDA, but due to limitations in both physical and in vivo properties, their uses remain largely confined to craniofacial and selected non-load bearing orthopedic applications. Through the following Aims, the objective of the present proposal is to determine how to build into CPC materials those attributes that are of critical importance for different applications so that CPC materials can be useful for a wider range of clinical applications. Aim 1. To develop and study the properties of CPCs that form products comprising a wide range of phase compositions and resorption rates suitable for different clinical applications. Aim 2. To develop and study the properties of elastomeric CPC materials that would provide compliance for micro-motions within the tissues and resist fracturing. Materials with these properties should be useful for applications such as periodontal defect repair, ridge augmentation, and spinal fusion. Aim 3. To develop and study the properties of rapid setting moldable/injectable premixed CPCs that are stable in the package and harden at tissue defect site. These CPCs can be more easily delivered to the defect site and possibly with reduced surgical invasions. Aim 4. To evaluate in vivo properties of selected CPC materials developed in the first three Aims in animal models. The following three animal studies will be conducted: (1) Evaluation of in vivo resorption rates of new CPC materials developed in Aim 1 that exhibit a wide range of in vitro acid dissolution rates. The study will employ a dog model, and histopathological measurements and electron microprobe analyses will be used to obtain quantitative data on in vivo resorption/bone replacement rates. (2) Evaluation of in vivo characteristics of non-rigid CPCs developed in Aim 2. The study, employing a dog model, will focus on the biocompatibility and resorption and bone replacement of CPC-chitosan composites in which the CPC and chitosan components have closely matched in vitro acid dissolution rates. (3) Evaluation of premixed, injectable CPC in a dog model to determine biocompatibility and osteoconductivity of these materials, which contain non-calcium phosphate components that have not been evaluated in vivo in previous studies.